The long range goal of this research is to increase the efficacy of topical therapy of human enamel. Incorporation of fluoride in enamel from systemic ingestion of fluoride is in the form of fluorapatite and is caries preventive. It is reasoned that maximal fluorapatite formation from topical treatment is beneficial. Consequently, we propose to study factors which (1) affect fluoride penetration into the enamel and (2) enhance fluorapatite formation within the enamel. Further, we propose to demonstrate in vivo the validity of the in vitro research using the hamster as a model. Fluoride penetration into enamel during topical fluoride therapy is known to be associated with dissolution and precipitation reactions which are affected by a number of factors including solution acidity and the fluoride salt used. Fluorapatite formation is enhanced when certain ions such as orthophosphate are present in the treatment solutions. We have developed chemical techniques that are applicable to the determination of the rate of fluoride penetration into the enamel, fluorapatite formation and to the determination of the amount of space occuppied by such reaction products as calcium fluoride. We have shown that it is possible to affect the penetration of fluoride into the enamel by affecting the dissolution or precipitation rates through variations in acidity, choice of fluoride salt or use of surface active agents. We are therefore convinced that it is possible to formulate a topical fluoride solution with orthophosphate and/or another compound so as to optimize fluoride penetration and fluorapatite formation. We propose to use scanning electron microscopy in addition to the methods mentioned above to evaluate the results and finally to test the most promising treatment approaches in the hamster. We believe there is a great need for effective topical fluoride therapy among the over 100 million Americans who do not share in the benefit of consuming fluoridated drinking water.